A POTENT SYNTHETIC DECAPEPTIDE ANALOGUE OF LUTEINIZING HORMONE-RELEASING HORMONE (LHRH), ALSO KNOWN AS A GONADO-TROPIN RELEASING HORMONE (GNRH) AGONIST ANALOGUE, ACTS AS A POTENT INHIBITOR OF PITUITARY GONADOTROPIN SECRETION WHEN ADMINISTERED IN THE BIODEGRADABLE FORMULATION. FOLLOWING INITIAL ADMINISTRATION IN MALES, ZOLADEX CAUSES AN INITIAL INCREASE IN SERUM LUTEINIZING HORMONE (LH) AND FOLLICLE STIMULATING HORMONE (FSH) LEVELS WITH SUBSEQUENT INCREASES IN SERUM LEVELS OF TESTOSTERONE. CHRONIC ADMINISTRATION OF ZOLADEX LEADS TO SUSTAINED SUPPRESSION OF PITUITARY GONADOTROPINS, AND SERUM LEVELS OF TESTOSTERONE CONSEQUENTLY FALL INTO THE RANGE NORMALLY SEEN IN SURGICALLY CASTRATED MEN APPROXIMATELY 2-4 WEEKS AFTER INITIATION OF THERAPY. THIS LEADS TO ACCESSORY SEX ORGAN REGRESSION.
IN FEMALES, A SIMILAR DOWN-REGULATION OF THE PITUITARY GLAND BY CHRONIC EXPOSURE TO ZOLADEX LEADS TO SUPPRESSION OF GONADOTROPIN SECRETION, A DECREASE IN SERUM ESTRADIOL TO LEVELS CONSISTENT WITH THE POSTMENOPAUSAL STATE, AND WOULD BE EXPECTED TO LEAD TO A REDUCTION OF OVARIAN SIZE AND FUNCTION, REDUCTION IN THE SIZE OF THE UTERUS AND MAMMARY GLAND, AS WELL AS A REGRESSION OF SEX HORMONE-RESPONSIVE TUMORS, IF PRESENT. SERUM LH AND FSH ARE SUPPRESSED TO FOLLICULAR PHASE LEVELS WITHIN FOUR WEEKS AFTER INITIAL ADMINISTRATION OF DRUG. CLINICAL STUDIES SUGGEST THE ADDITION OF HORMONE REPLACEMENT THERAPY (ESTROGENS AND/OR PROGESTINS) TO ZOLADEX IS EFFECTIVE IN REDUCING THE BONE MINERAL LOSS WHICH OCCURS WITH ZOLADEX ALONE ( IN FEMALES ).